Comparative Long-Term Clinical Performance of Mechanical Aortic Valve Prostheses

Key Points Question Is there a difference among bileaflet mechanical aortic valve prostheses in the long-term incidence of all-cause mortality, aortic valve reintervention, heart failure, major bleeding, stroke, and embolic events? Findings In this cohort study of 5224 patients who underwent surgical aortic valve replacement in Sweden between 2003 and 2018, the Bicarbon valve had a significantly higher incidence of 10-year all-cause mortality (27%) than the Carbomedics (17%), Regent (17%), and Standard (17%) valves. Otherwise, the performance was generally comparable among the different valve groups. Meaning This study suggests that further studies on the long-term performance of the Bicarbon valve are warranted.


Introduction
Aortic valve replacement with mechanical valve prostheses has been performed since the 1950s. 1 However, in the past 2 decades, the use of mechanical valves has decreased in favor of bioprosthetic valves across all age groups. 2,3This shift can most likely be attributed to the fact that patients who undergo a mechanical valve implant require lifelong warfarin treatment, which subsequently increases the risk of adverse anticoagulation-related events. 4,5In addition, improvements in the durability of biological valves have contributed to their increased use.According to European guidelines, mechanical valves are the recommended choice for patients younger than 60 years, 6 whereas US guidelines recommend mechanical valves for patients younger than 50 years. 7

Key Points
Question Is there a difference among bileaflet mechanical aortic valve prostheses in the long-term incidence of all-cause mortality, aortic valve reintervention, heart failure, major bleeding, stroke, and embolic events?

Study Population
Patients who underwent surgical aortic valve replacement (SAVR) with mechanical aortic valves between January 1, 2003, and December 31, 2018, in Sweden, with or without concurrent coronary artery bypass grafting surgery or ascending aortic surgery, were included.The exclusion criteria were being younger than 18 years of age, undergoing concurrent surgery on another valve, undergoing surgery with the use of deep hypothermia or circulatory arrest, having undergone cardiac surgery or transcatheter aortic valve replacement, use of a tilting-disk or ball-in-cage prothesis, or undetermined prosthesis type.

Exposure and Outcomes
The exposure was defined as having received a prosthetic mechanical aortic valve.The following valve model groups were analyzed in the study: On-X, Carbomedics, Bicarbon, Standard, Regent, Open Pivot, Masters, and Advantage.A few valve models were excluded due to low rates of use.The frequencies and types of valves within each valve model group are presented in eTable 1 in Supplement 1.The primary outcome was all-cause mortality, identified from the Total Population Register. 12The secondary outcomes were aortic valve reintervention (identified from the Swedish Cardiac Surgery Registry 13 ); heart failure hospitalization; bleeding; and stroke, transient ischemic attack (TIA), or embolic event, all identified from the national patient register through International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes 14 (codes used to identify the secondary outcomes in the National Patient Register are presented in eTable 2 in Supplement 1).

Data Sources
The Swedish Cardiac Surgery Registry, part of the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) Register, was used to identify the study population. 15The Swedish Cardiac Surgery Registry collects preoperative, perioperative, and postoperative data on all cardiac surgery patients nationwide with high reliability. 13The National Patient Register was used to collect baseline characteristics of preexisting morbidities, as well as outcome data for the heart failure;

JAMA Network Open | Cardiology
transcatheter aortic valve implant reintervention; bleeding events; and stroke, TIA, and embolic events.The National Patient Register has full coverage of all inpatient diagnoses in Sweden and has high validity. 14The longitudinal integrated database for health insurance and labour market studies register 16 was used to obtain the socioeconomic baseline characteristics of the study population.The Swedish personal identity number enabled cross-linking between the registers. 17

Statistical Analysis
Statistical analysis was performed between May and September 2023.Baseline characteristics are described as mean (SD) values for continuous variables.Categorical variables are described as frequencies and percentages.Baseline differences between the groups were described as standardized mean differences as estimated by the R package tableone (R, version 4.1.0;R Project for Statistical Computing).Time to event was determined as the time in days from the date of surgery to the date of event or the end of follow-up on December 31, 2018.A Poisson model was used to estimate age-and sex-adjusted incidence rates.The Aalen-Johansen estimator was used to estimate the crude cumulative incidence while accounting for the competing risk of death.Flexible parametric regression standardization was used to estimate cumulative survival while adjusting for the distribution of covariates in the population. 18The resulting survival curve is an estimate of population survival if the entire population had received the same of each respective valve.Flexible hazardbased regression standardization as described by Kipouro et al 19 was used to estimate cumulative incidence of reintervention; heart failure hospitalization; bleeding events; and stroke, TIA, or embolic events.This method adjusts for the population distribution of covariates while accounting for the competing risk of death.The resulting cumulative incidence curve can be interpreted as the estimated cumulative incidence if the whole study population received the same of each valve model.Model selection was performed using clinical subject matter knowledge and was guided by the Akaike information criterion.Covariates included in the different models are presented in the eMethods in Supplement 1. Missing data were handled with the classification and regression tree estimation and imputation approach (eMethods in Supplement 1). 20Data management and statistical analyses were performed using R, version 4.1.02][23][24][25] All P values were from 2-sided tests and results were deemed statistically significant at P < .05.

Results
We

Heart Failure Hospitalization
The total follow-up time for heart failure hospitalization was

Bleeding Events, Stroke, TIA, or Embolic Events and Sensitivity Analyses
Results regarding bleeding events, stroke, TIA, or embolic events are presented in the eResults and eFigures 9 and 10 in Supplement 1.The results of sensitivity analyses are presented in the eResults and eFigures 11, 12, 13, 14, and 15 in Supplement 1.

Missing Data
The

Discussion
In this large, population-based, nationwide cohort study, patients who underwent SAVR with the Bicarbon valve prosthesis had a higher mortality risk than patients who underwent SAVR with the Carbomedics, Regent, Masters, or Standard valve prostheses.Patients who underwent SAVR with a Standard, Regent, On-X, or Masters prosthetic valve had a higher risk of aortic valve reintervention than patients who received the Bicarbon or Open Pivot valve prostheses.Patients with a Carbomedics or On-X valve prosthesis had a higher risk of stroke, TIA, or embolic events than patients who received the Regent valve prosthesis.

Comparison of Multiple Valve Prosthesis Models
In the literature, prosthetic aortic valve model performance is typically studied either within a single valve model series or through direct comparison between 2 valve models. 26,27However, multiple valve models can be compared simultaneously using data from national registers, as suggested by Hickey et al, 8 allowing researchers to identify differences in performance among several valve models.Although these differences may be small in magnitude, they can still be of clinical significance.Swedish national health data registers enabled us to comprehensively assess the performance of all common mechanical aortic valve model prostheses within the same population, with long-term and complete or near-complete follow-up data.Within the Total Population Register, the primary outcome of mortality is tracked both nationally and internationally, ensuring complete follow-up. 12Regarding the secondary outcomes of reintervention; heart failure hospitalization; major bleeding events; and stroke, TIA, or embolic events, the only potential for loss to follow-up would arise if patients were to emigrate after undergoing cardiac surgery in Sweden, subsequently seeking further medical care abroad.Given Sweden's universal health care coverage, we consider this likelihood to be minimal, rendering the follow-up data nearly complete.Thus, the robust data sets  that can be obtained from Swedish registers present a unique opportunity to explore the concept of postmarket surveillance of prosthetic valve model groups within a Swedish cohort.

Valve Model Group Differences
Previous research compared bioprosthetic aortic valve model groups and observed notable differences in performance across these groups. 9However, in the present study, when contrasted with the findings of Hickey et al 8 and Persson et al, 9 the performance of mechanical aortic valves was largely consistent across the model groups, except for the Bicarbon model group with respect to all-cause mortality.In fact, the estimated differences in heart failure hospitalization and bleeding events were close to 0, indicating virtually no difference at all (eFigures 8 and 9 in Supplement 1).
The Bicarbon model group exhibited a significantly higher all-cause mortality rate than the Carbomedics, Regent, Masters, and Standard model groups.Moreover, given that the mortality differences between the Bicarbon group and the Carbomedics, Regent, Masters, and Standard groups were greater than 10% after 15 years (Figure 2), we interpret this result as reflecting a clinically significant difference in the performance of the Bicarbon valve.
[30][31] For example, Celiento et al 26 revealed a 17-year survival rate of 47.9% for the Bicarbon valve, along with a 1.9% reintervention rate over the same time period.Furthermore, a study examining hemodynamic performance differences among various valve models concluded that both the Bicarbon and the St Jude Hydrodynamic Plus valves outperformed the Carbomedics valve. 32ecifically, the Carbomedics valve exhibited higher gradients, along with lower effective orifice areas and performance indices at 60 days after surgery.Another in vitro study made similar observations, showing that the Bicarbon and St Jude Medical valves had superior hemodynamic profiles in terms of lower shear stress when compared with the Carbomedics and Edwards Duromedics valves. 33The superior hemodynamic profile of the Bicarbon valve does not appear to translate into better clinical outcomes.In the study by Hickey et al, 8 no significant differences were observed in terms of mortality or reintervention rates when comparing the Bicarbon valve with other valve models.The only standout finding in the mechanical valve category in their study pertained to the Medtronic Hall model group, which initially showed a larger unadjusted hazard; however, this difference was negated after statistical adjustments.
Regarding reintervention, we found that the Bicarbon and Open Pivot model groups outperformed the Standard, Regent, On-X, and Masters model groups.However, given the small number of events in these groups (1 in the Bicarbon group and 2 in the Open Pivot group), these results must be interpreted with caution.Similarly, the observed disparities in the outcome of stroke, TIA, or embolic events may be spurious.Among these groups, the Carbomedics and On-X model valves exhibited poorer performance than the Regent model valves.

Findings
In this cohort study of 5224 patients who underwent surgical aortic valve replacement in Sweden between 2003 and 2018, the Bicarbon valve had a significantly higher incidence of 10-year all-cause mortality (27%) than the Carbomedics (17%), Regent (17%), and Standard (17%) valves.Otherwise, the performance was generally comparable among the different valve groups.Meaning This study suggests that further studies on the long-term performance of the Bicarbon valve are warranted.

Figure 1 .
Figure 1.Regression Standardized Cumulative Incidence of All-Cause Mortality After Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018

Table 2 )
. The crude cumulative incidence and number of all-cause mortality events at 5, 10, and 15 years are presented in Table2.

Table 2 )
. The crude cumulative incidence and the number of events at 5, 10, and 15 years are presented in Table2.After regression standardization, the estimated cumulative incidence of reintervention at 10 years was lowest in the Bicarbon model group (0.8%; 95% CI, 0.1%-5.5%)and highest in the Masters model group (5.4%; 95% CI, 3.1%-9.1%)(eTable 4 in Supplement 1).There was a statistically significant difference between the Bicarbon and Open Pivot model groups, which both performed better than the Standard, Regent, On-X, and Masters model groups.The regression standardized cumulative incidences of reintervention at 5, 10, and 15 years are presented in eTable 4 in Supplement 1.The regression standardized differences in the cumulative incidence of aortic valve reintervention are shown in eFigure 7 in Supplement 1.

Table 2 .
Crude Cumulative Incidence and Events per PY for All-Cause Mortality, Reintervention, Heart Failure Hospitalization, Bleeding Event, and Stroke, TIA, or Embolic Event After Surgical Aortic Valve Replacement in Sweden Between 2003 and 2018 eTable 3 in Supplement 1).Age-and sex-adjusted incidence rates per 100 person-years were lowest in the On-X group (0.76; 95% CI, 0.54-1.08)and the Advantage group (0.76; 95% CI, 0.43-1.36)andhighest in the Bicarbon group (1.07; 95% CI, 0.90-1.27).The crude cumulative incidence for heart failure hospitalization at 10 years was lowest in the On-X model group (6.4%; 95 CI, 3.5%-9.4%)andhighestintheStandard group (15.3%; 95% CI, 11.9%-18.8%)(Table2).The crude cumulative incidence and the number of events at 5, 10 and 15 years are shown in Table2.After regression standardization, there was no statistically significant Abbreviations: NA, not available; PY, person-years; TIA, transient ischemic attack.aUsing Aalen-Johansen estimator accounting for the competing risk of death.( Masters model group and Bicarbon model group (A), between the Carbomedics model group and Bicarbon model group (B), between the Regent model group and Bicarbon model group (C), and between the Standard model group and Bicarbon model group (D).The shaded areas indicate 95% CIs.The dashed horizontal lines indicate 0% difference; if the 95% CI crosses this line, the difference is not significant.

eTable 4 .
Regression Standardized Cumulative Incidence for All-Cause Mortality, Reintervention, Heart Failure Hospitalization, Bleeding and Stroke, TIA or Embolic Event Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 % (95% CI) eFigure 1. Number of Implanted Mechanical Valve Prostheses per Model Group and Year in Sweden Between 2003 and 2018 eFigure 2. Age Distribution per Model Group After Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 3. Proportion of Prosthesis Valve Size per Model Group Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 4. Proportion of Left Ventricular Ejection Fraction at Surgery per Model Group Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 5. Proportion of Patient Sex per Model Group Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 6.The Regression Standardized Difference in Cumulative Incidence of All-Cause Mortality Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 7. The Regression Standardized Difference in Cumulative Incidence of Aortic Valve Reintervention Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 8.The Regression Standardized Difference in Cumulative Incidence of Heart Failure Hospitalization Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 9.The Regression Standardized Difference in Cumulative Incidence of Bleeding Events Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 10.The Regression Standardized Difference in Cumulative Incidence of Stroke, TIA or Embolic Event Following Surgical Aortic Valve Replacement With a Mechanical Valve Prosthesis in Sweden Between 2003 and 2018 eFigure 11.Kaplan-Meier Estimated Survival and Number at Risk After Surgical Aortic Valve Replacement With Different Mechanical Valve Model Groups in Sweden Between 2003 and 2018 eFigure 12. Aalen-Johansen Estimated Aortic Valve Reintervention and Number at Risk After Surgical Aortic Valve Replacement With Different Mechanical Valve Model Groups in Sweden Between 2003 and 2018 eFigure 13.Aalen-Johansen Estimated Heart Failure Hospitalization and Number at Risk After Surgical Aortic Valve Replacement With Different Mechanical Valve Model Groups in Sweden Between 2003 and 2018 eFigure 14.Aalen-Johansen Estimated Major Bleeding Event and Number at Risk After Surgical Aortic Valve Replacement With Different Mechanical Valve Model Groups in Sweden Between 2003 and 2018 eFigure 15.Aalen-Johansen Estimated Stroke, TIA or Embolic Event and Number at Risk After Surgical Aortic Valve Replacement With Different Mechanical Valve Model Groups in Sweden Between 2003 and 2018